Increased expression of monocyte chemotactic protein-1 during active hepatic fibrogenesis: correlation with monocyte infiltration.
Monocyte chemotactic protein (MCP)-1 is a chemoattractant and activator for circulating monocytes and T lymphocytes. We investigated MCP-1 protein and gene expression during chronic liver disease at different stages, using immunohistochemistry and in situ hybridization, respectively. In normal liver, a modest expression of MCP-1 was confined to few peri-sinusoidal cells and to bile duct epithelial cells. During chronic hepatitis, MCP-1 immunostaining and gene expression were evident in the inflammatory infiltrate of the portal tract. In tissue from patients with active cirrhosis, MCP-1 expression was clearly up-regulated and was present in the portal tract, in the epithelial cells of regenerating bile ducts, and in the active septa surrounding regenerating nodules. A combination of in situ hybridization for MCP-1 and immunohistochemistry showed that activated stellate cells and monocyte/macrophages contribute to MCP-1 expression in vivo together with bile duct epithelial cells. Comparison of serial sections of liver biopsies from patients with various degrees of necro-inflammatory activity showed that infiltration of the portal tracts with monocytes/macrophages is directly correlated with the expression of MCP-1. These data expand previous in vitro studies showing that secretion of MCP-1 may contribute to the formation and maintenance of the inflammatory infiltrate observed during chronic liver disease.
Marra
F
F
Istituto di Medicina Interna, Università di Firenze, Florence, Italy. f.marra@dfc.unifi.it
DeFranco
R
R
Grappone
C
C
Milani
S
S
Pastacaldi
S
S
Pinzani
M
M
Romanelli
R G
RG
Laffi
G
G
Gentilini
P
P
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D002908:Chronic Disease; D005260:Female; D006505:Hepatitis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018932:Chemokine CCL2; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule